A major clinicoepidemiological problem associated with Herpes simplex viruses (HSV) is that of recurrent infections. Current evidence indicates one of the major sites for latency in-between recurrences is the sensory ganglion. The proposed studies are aimed at obtaining further understanding of the basic mechanisms of HSV-1 latency in human trigeminal ganglia. Single cell type preparations of neuron cells and supporting cells will be used to define and enumerate the cells harboring the virus. The possible presence of Ig or Fc Ig receptors on the membrane of the different cell preparations, which might modulate virus reactivation, will be ascertained. Several methods will be employed to determine whether reactivation of virus from latency is influenced by the cell's metabolism and/or the status of the virus genome. These include: a) comparing the ability of HSV and poliovirus to replicate in freshly explanted cells or cells in culture for several days; b) the effect of cyclic nucleotide (cAMP and cGMP) enhancers, depolarizing factors, e.g. ouabain, and ts mutants to accelerate virus reactivation from latency. Information obtained from these studies should be applicable to HSV-2 and the infections produced by this virus type. The long-term goal is to find some means of preventing HSV recurrences which afflict at least one-third of our population and may, on occasion, be associated with severe disease.